第四章 血浆脂蛋白及其代谢紊乱 plasma lipoproteins and its metabolic disorder
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第四章 血浆脂蛋白及其代谢紊乱 Plasma Lipoproteins and Its Metabolic Disorder. 湘南学院医学检验系 临床生化检验教研室. 本章内容概要. 第一节 血浆脂蛋白结构与受体 第二节 脂蛋白代谢 第三节 脂蛋白代谢紊乱 第四节 脂蛋白代谢紊乱与 AS 第五节 血脂、脂蛋白及载脂蛋白测定. 教学目标. [ 掌握 ] 脂蛋白代谢紊乱(高脂血症分型及特征),血浆脂类及脂蛋白测定方法 。 [ 熟悉 ] 血浆脂蛋白的化学和正常代谢,载脂蛋白的结构与功能 。 [ 了解 ] 脂蛋白受体及代谢有关酶 。. - PowerPoint PPT PresentationTRANSCRIPT
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Plasma Lipoproteins and Its Metabolic Disorder
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AS
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[] [] [] [] 6
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951. 2. 3. 4. 5. 6. 51. 2. 3.
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(triglyceride, TG)
(free cholesterol,FC)
cholesterol ester, CE)
(TC)
(phospholipid, PL)
(free fatty acid, FFA)
() plasma lipids (glycolipid)
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1 +(TGPLFC+CE) (1) HDL>LDL>VLDL>CM CM>VLDL>LDL>HDL (2) (Apo)()
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2 ApoPL(PL) (TGCE)PL ApoPLFC Apo
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, TGCE PLFFA
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HDL LDL VLDL Lp(a) IDL
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CM VLDL LDL HDL CM - LP-LP-LP
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(ultra centrifugation method)(density-gradient method) Sf (Svedberg floatation rate)
Sf
d(g/ml)
CM
>400
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(electrophoresis method)
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TGrich LipoproteinChrich Lipoprotein
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CM, , CM (), AS
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VLDL
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LDL,ASASLDL
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HDL HDLAS,
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() ()
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()(apolipoproteinApo) 12 1972AlaupovicApoABCDEFGHJ
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apoAapoAapoAapoAapoAapoAapoAHDL
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apoBapoB100apoB48apoB100LDLapoB48CM
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apoCapoCapoCapoCapoCVLDLapoB100apoC apoD apoEapoE2apoE3apoE4
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3 LCATapoAapoAapoCapoALpLapoCapoAapoCHLapoA
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apoBapoBELDLapoEapoBEapoELDLLRPapoAHDL
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CETPHDLVLDLLDLPTPCMVLDLHDL apoDLCATapoAapoA-apoD-LCAT
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() genotype ()(Phenotype)
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1
( 1 )ApoAApoBApo(a)
(intron) 3
(exon) 4
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( 2) ApoACA112 ApoECC193
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2 ( 1 ) ApoA 1 863bp34 658bp ApoAApoA 11
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( 2 ) ApoB 2ApoB100 43kb2829 7 572bp39bp
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( 3 ) ApoE 1934 ApoE3 ApoE2ApoE3ApoE4 E2/2E3/3()E4/46 E2/3E2/4E3/4 ( 4 ) ApoC ApoCApoC3347bp 3133bp3,4
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( 5 ) Apo(a) 6 525kb1918 Apo(a)2634
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ApoCIApoA
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*A 11q23-qApoAA1 q23-q23ApoAA11ApoA(a)6Apo(a)B2q24-q23ApoBC19q13.2ApoCC19ApoCC11ApoCD 3ApoDE19q13.2ApoEH 17q23-qApoHJ8p21CL
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ApoEApoC ApoCII
19q311q2 , , , ApoCApoAApoAApoA
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LDLVLDL
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LDLLDL receptor 1974 LDL 1LDL 836115kD5
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2LDL1 coated pit ;
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(2) ApoB100ApoE ApoB-E ApoB48 LDLApoB100LDLLDL ApoB/ELDL
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3LDLLDL receptor pathway 1LDLApoB100EVLDL-VLDLLDLLDL-VLDLVLDL-LP CEApoApoEApoCVLDL
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2LDL LDL+LDL LDL-LDLcoated vesicles LDLLDLLDL Apo CE FFA+FC TG +FFA
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(3) FC Ch HMGCoA ACATCoAFCCE LDLLDLLDL
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4 LDLLDL VLDL CM LDLCMCMApoB48LDLApoEApoCLDLCM
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VLDL 1 LDL5 2 ApoEVLDL-VLDLApoB100LDL Ch
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3 VLDL-VLDL 4 1As 2
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scavenger receptor LDL LDL LDL AsLDL-CELDLLDLLDLLDLLDL
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1
220 ku,, LDLN-C-inside-out6N-C
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2 1LDL LDLLDLox-LDLAs 2
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3 LDLox-LDLAs LDL
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HDL(RCT) VLDL-IDL-LDLVLDL, IDLLDL,CMChTGCMLP
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(CM)
TG TGTG :
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CM
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()VLDL1.2.TG(50%-70%)ApoB100ChCM3.TG 4.
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VLDLHDL IDL
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VLDL TGVLDL
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() LDL1.VLDL2. Ch(45%-50%)CEHDL(CETP) APOApoB100 3.4. (1) LDL
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2 LDLLDLLDLLDL (ox-LDL)(scavenger receptor, SR)LDL* 45%LDL2/3LDL1/3
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LDL
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LDL
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LDL,LDLLDL
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()HDL 1. 2. 3. HDLApoEApoC HDLHDL 4.
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HDL
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HDLHDL3 HDL2 LCAT CETP
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Hyperlipoproteinemia Hyperlipidemia TG/TC
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:
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ApoLP WHOab
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()CM 1. 1LPL 2ApoC Apo C() LPL CMTG CMCM CM 2.
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3.14CM 2TG 3CM 4CM 5LPLLPLApoC
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()IIa1. LDL (1) LDL (2) LDLLDL (3) LDL LDLLDL LDLLDL-Ch AS
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2. ASAS3.12 TG34LDL ApoB
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() b-LP -LP 1.: ApoB100VLDLLDL 2. baLDL
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3. (1 2 TG 3LPPre LP 4 LDL VLDL
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() (-VLDL-) 1. ApoE ApoEApoE2E3E4ApoE(VLDL)E2VLDLApoE3/E3VLDLApoE2/E2VLDLVLDL
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2.AS3.1 2TG Ch 3-VLDL LPPre LP--VLDL4 IDL (-VLDL)
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() (TG VLDL) 1. VLDL/VLDL
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2.142 TG Ch 3 Pre 4 VLDL VLDL
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3.
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() (CM-LP) 1. ApoC LPL CMVLDL TG LPL
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2. 203050
3.12TG Ch 3CM 4CM VLDL
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() HDL HDLASASHDLHDL 1 HDL-Ch> 2.6mmol/L0.78-2.2mmol/L0.3-0.85g/L
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2 (1) CETPCETPHDL-CEHDL, HDL HTGL, HDL, HDL HDL, HDL-ch(3~5) (2)
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CETP HTGL HDL HDL-C2.6mmol/LHDL CETPHTGLHDL
HDL
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(secondary hyperlipoproteinemia) () , () () ()
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VLDLLPLCMVLDLTG TG
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ab: LPL,VLDL; HTGL,IDL; LDL,LDL
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Cushing VLDLVLDLLDLa b
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ApoBVLDLVLDLLDLb LPLVLDL
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AS AS HDLAS
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ASASLDL-VLDL oxLDLAS HDLAS AS
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AS
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CMVLDLLPLCMIDLApoE -VLDL(ApoE)-VLDLASAS
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LDL LDLLDLLDL,LDL: LDL LDL LDL LDLApoB100LDLLDLAS
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LDL-CAS LDLAB: B(LDL)AS,BLDL,LDLLDLCHD LDL(SD-LDL) BLDL
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(a)LP-(a)Lipoprotein(a) 1963LDL
TGPLFCCE ApoB100Apo(a)()
LDL
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LP(a)As,Apo(a)As
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1 2LDL 3 4 5 6 HDLAS
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HDLApoAIApoB
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HDL: CENCEHFCHDLNCEH FC: NCEH NCEH
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ASAS
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TCTGHDL-CLDL-C ApoAIApoBLpa TCTGHDL-CLDL-C 4 TCTG
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CDC
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12h4
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() (CEH)(cholesterol oxidaseCOD)4H2O2(POD) H2O24-(4AAP)(PAP)500nm
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-4060001-2 C
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2.85.2mmolL
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112020405070234
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21TC - CoA 2TC
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() -----GPO-PAP
C
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0.55-1.70mmol/L 2.30mmol/L 4.50mmol/LTG
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1TG TGCHDTG 2TG
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() .
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()---LDLVLDLLp(a)HDL(TC)HDL(HDL-C)HDLTGpH4h
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HDL-C 0.9mmol/L
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:(1)HDL-CHDL-C0.9mmolL(2)HDL-C(3)TGHDL-C4HDL-C5HDL-C6HDL-C
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()-----Friedewald
LDL-CTCHDL-CTG2.2(mmolL) FriedewaldLDL-CTCTGHDL-CLDL-C CMTG>4.52mmolL(400mgd1)-FriedewaldLDL-C
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LDL-C 2.13.1mmol/L 2.8mmol/L
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: LDL(LDL-C)LDLLDL-CTCLDL-CLDL-CLDL-C
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AIB ApoAIApoBApoAApoBApoAIApoBApoAIApoB
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ApoAI1.00~1.50gLApoB0.80~1.00gL
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ApoAIHDLHDLApoBLDLLDLLDLApoAIApoB,HDL-CLDL-CApoAIApoBApoAIApoB
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1 2ApoAAB100 C 3LDL??LDL??? 4CM VLDL LDL HDL 5? 6? 7APOA1APOB100HDLLDL
1.063g/ml(1.75mol/L Nacl)1.063 1.063(HDL) Sf LDL VLDLLDL LDL VLDLLDL
1 ApoB100/ApoE,ApoB100ApoELDLligand VLDLVLDL-VLDL2EGF 3 4 5 C- LDL,LDLLDL